Implications of Aspirin for Melanoma Treatment: A Short Perspective
نویسندگان
چکیده
Despite various available treatment options, the prognosis of melanoma remains grim [1]. This indicates the involvement and cross talks between several oncogenic signaling pathways including the driver mutations in central BRAF and NRAS genes leading to increased heterogeneity and resistance of melanoma tumors to targeted therapies [2]. Among other signaling cascades, activation of a G-protein coupled receptor in response to oxidized phospholipid mediator, platelet-activation factor (PAF) produced by several pro-oxidative stressors generating reactive oxygen species (ROS) plays important roles in favoring the growth of pre-existing melanoma tumors in preclinical studies [3-14]. Importantly, studies including ours have demonstrated that PAF and PAF-like species possess immunosuppressive properties and induce systemic immunosuppression that results in an augmentation of subcutaneously implanted murine B16F10 melanoma tumors growth via increasing regulatory T-cells (Tregs) in tumor microenvironment [6,10,11]. Notably, we have shown that therapeutic agents including cancer chemotherapy generate PAF agonists as a byproduct that augment the growth, and impede their efficacies in a PAF-receptor (PAF-R) dependent manner in experimental murine melanoma models [7,8]. Of significance, increased levels of PAF or PAF-R activity were detected in melanoma patients undergoing therapeutic treatments [7,8]. As melanomas express COX-2 enzyme which is the downstream target of PAF-R signaling pathway, we have shown that COX2 inhibition blocked PAF-R mediated effects of pro-oxidative stressors including cancer therapies in preclinical studies [3,7-9]. These findings indicate crucial roles of PAF-R signaling in melanoma tumorigenesis and melanoma therapies.
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تاریخ انتشار 2017